Cell competition: New insights into tumor formation and E-cadherin!

Cell competition: New insights into tumor formation and E-cadherin!

The complexity of multicellular organisms, especially in humans, is reflected in the multitude of cell types that have specific properties and functions. Deviations from this evolutionary blueprint are not just theoretical concepts, but can have serious consequences, such as developmental disorders and illnesses. Mechanisms for quality control of cell aggregates are therefore essential to maintain the integrity of tissues and organs. FAU reports that a central mechanism known as “cell competition” summarizes these surveillance processes and ensures the health of the cell community.

Cells in a tissue constantly adapt their properties to those of their neighbors by comparing their fitness levels. In this competition, the “winner” cells survive while the “loser” cells die. Failure of these control mechanisms can have serious consequences, including tumor formation. An international research team recently identified a new strategy that enables winning cells to emerge in mechanical cell competition. These cells can successfully transfer high mechanical forces to their surroundings and thus gain a decisive competitive advantage.

Mechanical forces and tumorigenesis

The study showed that high mechanical force fluctuations occur at the interfaces between mutant and healthy cells, which are crucial for the elimination of less efficient cells. This calls into question the assumption that winner cells only cause the death of loser cells by compressing them. Rather, the competitive advantage is based on the cells' active resistance to their elimination. Additional research emphasize that the cell-cell adhesion protein E-cadherin plays a crucial role in these processes.

Prof. Benoît Ladoux and his team are investigating in detail the connections between adhesion, mechanical signal transmission and biochemical processes. This combination of mechanical measurements and biological interventions has provided crucial clues about the role of E-cadherin. Surprisingly, the results show that cells are not systematically eliminated under high mechanical pressure, suggesting complex mechanisms of cell interaction.

Influence of E-cadherin on metastasis

The metastatic ability of E-cadherin-expressing tumor cells was also examined. Research has shown that downregulation of E-cadherin's adhesive activity is crucial, not the amount of the protein. This raises questions about the treatment of cancer and the influence of monoclonal antibodies. These antibodies enhance the adhesive activity of E-cadherin, which could influence the metastasis of E-cadherin-positive cells. In studies with the 4T1 mouse mammary carcinoma cell line, it was found that the use of activating monoclonal antibodies resulted in significant differences in the number of metastases.

In the control of mesh transfer and cell adhesion, a significant decrease in metastatic cells was observed in mice treated with activating antibodies. These results suggest that activation of E-cadherin adhesion inhibits metastatic progression, while primary tumors showed no significant differences in proliferation or E-cadherin expression.

Additionally, research is also investigating germline HDCG mutations in E-cadherin, which are associated with diffuse gastric cancer. These mutations affect cell adhesion and its activation, with some mutations significantly affecting adhesion. These findings open up new perspectives for research into tumor biology and offer starting points for therapeutic measures.

The comprehensive analysis of such complex biological processes could have significant implications for the treatment and understanding of diseases such as cancer, acute inflammation and other biological phenomena.